There has been a lot of confusion and misinformation regarding the true incidence of celiac disease and gluten intolerance. One of the reasons for this is an inconsistent use of the nomenclature and/or inappropriate use of terms such as allergy, intolerance, sensitivity and/or celiac disease. (We have chosen to define the most commonly used terms in Table 1). It is now known that gluten-intolerance appears to be an entire spectrum ranging from delayed-hypersensitivity reactions of gluten-sensitivity to true IgE wheat allergies, as well as autoimmune conditions such as celiac disease.1

Prevalence of celiac disease is now thought to exceed one percent of the population in international studies and gluten-sensitivity incidence is thought to be closer to six percent.2

What is Gluten?

Before I take a look at the different conditions associated with reactions to gluten, it’s important to define gluten and other similar proteins.

Gluten is actually a term used to describe a mixture of proteins found in grains. Gliadin makes up the majority of the protein in wheat gluten,3 Glutenin is another major protein found in gluten. These proteins, as well as lectins (other important proteins found in grains) are known to cause problems with digestion and allergy in humans similar to glutens.4 Wheat-germ agglutinin, although not technically a gluten, but instead a lectin, has been shown to have an inflammatory effect and cause direct damage to specific body tissues.4

An Allergy By Any Other Name…

Wheat Allergy is actually quite rare and involves an IGE immediate type response. IGE type of reactions are occur like when stung by a bee or wasp, that can cause airway issues and swelling of the skin, face and eyes., usually within minutes to hours after exposure. Conditions in this category are divided by route of exposure and location of reaction: skin, GI or respiratory tract. Wheat allergy can produce symptoms from mild urticaria and asthma to anaphylaxis. (any emergency type allergic reaction). 1 The term ‘allergy’ is not an IGE mediated type reaction as described above and has been used inappropriately to describe gluten sensitivity.

Immune-mediated gluten reactions take hours to days to manifest after initial exposure. Classified under this umbrella is gluten sensitivity (GS). There is evidence to suggest that IgG involvement,5 or the innate immune system, may be important in the development of GS.This is frequently referred to as gluten intolerance as well.

This condition is often associated with extra-intestinal symptoms, including neuropsychiatric symptoms (such as depression, anxiety, bipolar and schizophrenia like behavior), and varied reactions from headaches to abdominal pain to joint pain. However, abdominal symptoms similar to celiac disease can be present. The symptoms of gluten sensitivity can be varied, affecting seemingly unrelated systems.1 The term gluten-sensitivity is sometimes used as an umbrella term to describe the entire spectrum of gluten/wheat reactivity.

Autoimmune reactions to gluten can take weeks to years to develop after initial exposure and include the conditions of celiac disease and dermatitis herpetiformis,a unique reaction due to gluten, as well as gluten ataxia.(difficulty walking) These reactions are often associated with IGA-mediated cellular damage and activation of both the innate and adaptive immune systems.

Symptoms can be varied, but characteristic is steattorhea,(fatty whitish stools) diarrhea, failure to thrive, abdominal pain, malabsorption syndromes, blistering rash and cerebellar dysfunction resulting in ataxia.1 It is believed that celiac disease develops as a result of genetic susceptibility, environmental exposure and vulnerability, followed by immunological-based inflammation, which leads to autoimmunity.

Subclinical celiac disease is a term with various definitions and has been used to describe gluten sensitivity, latent celiac disease, atypical celiac disease and gluten-related non-celiac disorders. This term is confusing at best and is best replaced with the more specific definitions listed above, or explained in context.

Diagnostic Criteria

The criteria for diagnosing Celiac disease has changed drastically in the last 50 years. Original criteria for diagnosis in 1960 includeddamage to the intestinal lining.. This was usually improved by adoption of a gluten-free diet.

Antigliadin antibody presence was discovered in 1961, and the immune-mediated theory developed. In 1966, Marks linked dermatitis herpetiformis to gluten-sensitive enteropathy (GSE), and discovered that skin involvement could exist independent of evidence of GSE. This led to the discovery that celiac disease may be present, even in the absence of damage to the small intestine.6

Diagnostic criteria for gluten sensitivity is still under development, as can be seen in Table 1. There is no definitive test for it at this time.

Current trends use a four out of five rule or an algorithm to correctly diagnose celiac disease. The four of five rule means that at least four out of the following five criteria must be met in order to diagnose celiac disease:16

1. Positivity of serum celiac disease immunoglobulin based on a blood test.

2. Elevated immune response

3. Positive gene testing

4. Celiac enteropathy at the small bowel biopsy.

5. Response to the gluten-free diet.

One of the current diagnostic algorithms can be seen in Figure 1.

Dangers of Exposure

The dangers of exposure to gluten range from completely asymptomatic unknown effects to full anaphylaxis and even possible death. Most folks, however, experience common reactions such as GI discomfort, blistering rashes, malabsorption, weight loss and psychological or neurologic symptoms. Failure to thrive is commonly seen in children.

Other common associated conditions include:10,12

• Increased intestinal permeability

• Nutrient deficiencies and malabsorption

• Non-specific arthritic symptoms and aches and pains

• Diarrhea/steattorhea

• Skin issues such as dermatitis, herpetiformis and possible loss of skin pigment and swelling of lips and eyes.

• Cross-reactivity to other foods and tissue-specific antigens, which may lead to autoimmunity

Gluten-Sensitivity and Mental Illness

Gluten antibodies have been identified in schizophrenics in higher numbers than in the general population. For these schizophrenic patients showing elevated antibodies, there is no apparent gut involvement. Yet, they are often aided by a gluten-free diet.8

Furthermore, studies have shown that, despite the presence of anti-gluten antibodies, they do not appear to react the same as in celiac disease.8 Therefore, it is postulated that the presence of these antibodies may be more likely due to a shared increased gut permeability.10 There is also a link between celiacs being at greater risk for developing schizophrenia. Additionally, the incidence of CD is higher in schizophrenic populations, suggesting there may be a shared connection that is not yet fully understood.11

There have also been case studies showing psychosis in certain susceptible individuals where adherence to a gluten-free diet was an effective therapy.17 Screening individuals for gluten-intolerance spectrum disorders who are suffering from mental illnesses that have shown an association such as autistic spectrum disorders, schizophrenia, psychosis, etc. is warranted.

Cross Reactivity of Other Foods

Some peopleare described as having refractory celiac disease despite strict adherence to a gluten-free diet. In these individuals, it is believed that there may be a cross-reactivity between the immune reactions to gluten and other gluten-free foods. Indeed, the results of this study can be seen in Table 2. Some of these reactions were found to be due to actual gluten-contamination, as in instant coffee, while in others, it was a case of cross-reactivity based on similar amino acid sequences in the proteins.12

Treatment Options

For those with overt celiac, a lifetime implementation of a strict gluten-free diet is required. Depending on the length and severity of their disease process, they may also require nutrient replacement, treatment for reducing gut permeability and encouraging mucosal repair. It is also proper to give adequate nutritional counseling and discourage patients from simply substituting bread, cake, cereals and cookies with gluten-free alternatives.

Gluten-free products are often high-glycemic, low-fiber, nutrient-poor foods and should be used sparingly. Instead, recommend a healthy, plant-based, naturopathic diet with good, whole food choices, and to replace wheat and gluten with grains such as quinoa, gluten-free oats, beans and the like.

It is worth mentioning the possibility of cross-reactivity and the encouragement of having patients keep a food diary or consider testing for cross-reactivity to other foods if their symptoms persist after adoption of a gluten-free diet. It is also worth mentioning that, when the craving hits for baked goods, making them from a paleolithic diet perspective by using coconut and/or almond flours, which are more nutritious and fiber-rich than the gluten-free mix alternatives that often loaded with potato, corn or rice starches.

For those with gluten sensitivity, a gluten-free diet is recommended. However, some people may be able to tolerate trace amounts of gluten without apparent harm. The evidence for this is still not yet clear.

Nutrient Support

L-Glutamine has been shown to reduce intestinal hyper-permeability, support restoration of gut integrity18 and stimulate intestinal cell proliferation.19

Cabbage leaf releases lysophasphatidic acid, a wound-healing lipid, when it is digested. This lipid has been shown to be effective in healing the digestive tract.20

N-acetyl glucosamine has been shown to protect the intestinal lining from wheat proteins. This may be very useful as the patient adapts to strict adherence to a gluten-free diet and may help protect against accidental exposures.21

Marshmallow, a mucilaginous herb, has been shown to be soothing to mucous membranes, aid in intestinal healing22 and reduce inflammation.23

Probiotics may reduce the damage caused by eating gluten-containing foods and may improve mucosal healing after a gluten-free diet has started.24

Conclusion

When evaluating patients, doctors need to take into account the various symptoms and presentations that exist regarding the gluten-reactivity spectrum. A patient may be susceptible or symptomatic, even when they do not fit the current diagnostic criteria as it is still clearly evolving.

Consistent and clear use of nomenclature needs to be addressed so that there can be interdisciplinary cooperation, both in research and clinically, in our pursuit of health in regards to gluten-related illness. Proper treatment protocols need to address nutrient deficiencies, probiotic support and reduction in intestinal permeability in celiacs. Patients need ongoing support to adhere to a gluten-free diet, and family members may need to be involved.

Action Steps:

Gluten Reactivity Spectrum

A sensitivity to gluten or outright celiac disease can be the reason for your symptoms, including the numerous conditions mentioned in this article such as GI discomfort, skin disorders, psychological or neurologic symptoms and non-specific arthralgias and fibromyalgia. Here are some ways to determine if gluten is indeed the problem, and how to thrive if you are sensitive to gluten.

Use either the four out five rule or the algorithm method to achieve a satisfactory diagnosis.

Initial testing for celiac disease should include Ab testing for Ttg, anti-endomysial antibody and total IgA.

Treatment should include dietary education, a gluten-free diet and follow up with a GI specialist to monitor level of damage to intestinal lining when present.

Recognize that some patients, although antibody negative, may still present with villous atrophy.

Nutrients that can be helpful include:

L-glutamine

Cabbage leaf

N-acetyl glucosamine

Marshmallow

Probiotics

TABLES:

Table 2: Cross-Reactivity

Common Foods Antigens that

Can Cross-react

Common Tissue Antigens that

Can Cross-react

Dairy

Yeast

Corn

Oats

Millet

Rice

Most likely targets of later developing autoimmunity

Other foods should also be considered, Some foods are often known to be contaminated with trace amounts of gluten, such as instant coffee. Also, some countries allow products to contain gluten in trace amounts and still be labeled gluten-free.

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